Activation of the alternative complement pathway: recognition of surface structures on activators by bound C3b
Pangburn, M.K.; Morrison, D.C.; Schreiber, R.D.; Müller-Eberhard, H.J.
Journal of Immunology 124(2): 977-982
1980
ISSN/ISBN: 0022-1767 PMID: 7356723 Document Number: 156156
A soluble lipopolysaccharide (LPS) was isolated from Escherichia coli strain 04 and after mild alkaline hydrolysis was incorporated into the membrane of sheep erythrocytes (Es) which do not activate the alternative complement pathway. Modified cells were found to activate the pathway. The ability to create an activating surface by incorporation of a foreign molecule allowed examination of the mechanism of activator recognition by surface-bound C3b. When C3b was first deposited on the surface of Es and varying amounts of LPS subsequently were incorporated into the membrane, a dose-dependent decrease in binding of the control protein .beta.1H to C3b was observed. The maximum effect required approximately 120,000 monomer LPS molecules per cell carrying 20,000 C3b molecules. No decrease in Factor B binding to C3b occurred, demonstrating the specificity of the effect. Concomitantly, the functional half-life of the cell bound C3b exposed to the serum control proteins was increased 3-fold. Sialic acid appears to play no role in this mechanism, since the LPS did not contain this carbohydrate and the sialic acid content of Es was not altered by LPS incorporation. Cell bound C3b processes a recognition site distinct from the metastable binding site of C3b and that allows discrimination between nonactivating and activating surfaces. Surface structures (.beta.1H antagonists) that interact with the discriminatory site on C3b restrict alternative pathway control and activate the pathway.